Low concordance between QIAreach QuantiFERON-TB, a novel interferon-gamma release assay, and QuantiFERON-TB Gold Plus, in a population-based survey in Blantyre, Malawi.

Unlabelled: Urgent improvements in the diagnosis and management of infection are required to reach End TB goals. Conventional interferon-gamma release assays (IGRAs), such as QuantiFERON-TB Gold Plus (QFT-Plus), require substantial laboratory infrastructure and large blood volumes, limiting use in high-burden settings. The QIAreach QuantiFERON-TB (QIAreach QFT) was developed to overcome these challenges but has not previously been evaluated in field conditions in a low-income, high-burden country, or at scale in children.

Early user perspectives on using computer-aided detection software for interpreting chest X-ray images to enhance access and quality of care for persons with tuberculosis.

Despite 30 years as a public health emergency, tuberculosis (TB) remains one of the world's deadliest diseases. Most deaths are among persons with TB who are not reached with diagnosis and treatment. Thus, timely screening and accurate detection of TB, particularly using sensitive tools such as chest radiography, is crucial for reducing the global burden of this disease.

Community-based active-case finding for tuberculosis: navigating a complex minefield.

Community-based active case finding (ACF) for tuberculosis (TB) involves an offer of screening to populations at risk of TB, oftentimes with additional health promotion, community engagement and health service strengthening. Recently updated World Health Organization TB screening guidelines conditionally recommend expanded offer of ACF for communities where the prevalence of undiagnosed pulmonary TB is greater than 0.5% among adults, or with other structural risk factors for TB.

Overexpression of enhanced yellow fluorescent protein fused with Channelrhodopsin-2 causes contractile dysfunction in skeletal muscle.

Skeletal muscle activation using optogenetics has emerged as a promising technique for inducing noninvasive muscle contraction and assessing muscle function both in vivo and in vitro. Transgenic mice overexpressing the optogenetic fusion protein, Channelrhodopsin 2-EYFP (ChR2-EYFP) in skeletal muscle are widely used; however, overexpression of fluorescent proteins can negatively impact the functionality of activable tissues. In this study, we characterized the contractile properties of ChR2-EYFP skeletal muscle and introduced the ChR2-only mouse model that expresses light-responsive ChR2 without the fluorescent EYFP in their skeletal muscles.

Urine-Xpert Ultra for the diagnosis of tuberculosis in people living with HIV: a prospective, multicentre, diagnostic accuracy study.

Background: Diagnostic delays for tuberculosis are common, with high resultant mortality. Urine-Xpert Ultra (Cepheid) could improve time to diagnosis of tuberculosis disease and rifampicin resistance. We previously reported on lot-to-lot variation of the Fujifilm SILVAMP TB LAM.

Impact of active case finding for tuberculosis with mass chest X-ray screening in Glasgow, Scotland, 1950-1963: An epidemiological analysis of historical data.

Background: Community active case finding (ACF) for tuberculosis was widely implemented in Europe and North America between 1940 and 1970, when incidence was comparable to many present-day high-burden countries. Using an interrupted time series analysis, we analysed the effect of the 1957 Glasgow mass chest X-ray campaign to inform contemporary approaches to screening.

Methods And Findings: Case notifications for 1950 to 1963 were extracted from public health records and linked to demographic data.

Respiratory symptoms after TB treatment completion: A qualitative study of patient and provider experiences in urban Blantyre, Malawi.

Pulmonary tuberculosis (PTB) survivors experience a high burden of residual and recurrent respiratory symptoms after TB treatment completion. However, guidelines for the investigation and care of symptomatic TB-survivors are limited. We used qualitative methods to explore patient and provider understandings, experience and practice around respiratory symptoms in the post-TB period.

A prospective evaluation of the diagnostic accuracy of the point-of-care VISITECT CD4 Advanced Disease test in seven countries.

Background: CD4 measurement is pivotal in the management of advanced HIV disease. VISITECT® CD4 Advanced Disease (AccuBio Limited, Alva, UK; VISITECT) is an instrument-free, point-of-care, semi-quantitative test allowing visual identification of a CD4 ≤200 cells/µl, or >200 cells/µl from finger-prick or venous blood.

Methods: As part of a diagnostic accuracy study of FUJIFILM SILVAMP TB LAM (clinicaltrials.

Treatment preferences among people at risk of developing tuberculosis: A discrete choice experiment.

Diagnosing and treating people with bacteriologically-negative but radiologically-apparent tuberculosis (TB) may contribute to more effective TB care and reduce transmission. However, optimal treatment approaches for this group are unknown. It is important to understand peoples' preferences of treatment options for effective programmatic implementation of people-centred treatment approaches.

Prospective multicentre accuracy evaluation of the FUJIFILM SILVAMP TB LAM test for the diagnosis of tuberculosis in people living with HIV demonstrates lot-to-lot variability.

There is an urgent need for rapid, non-sputum point-of-care diagnostics to detect tuberculosis. This prospective trial in seven high tuberculosis burden countries evaluated the diagnostic accuracy of the point-of-care urine-based lipoarabinomannan assay FUJIFILM SILVAMP TB LAM (FujiLAM) among inpatients and outpatients living with HIV. Diagnostic performance of FujiLAM was assessed against a mycobacterial reference standard (sputum culture, blood culture, and Xpert Ultra from urine and sputum at enrollment, and additional sputum culture ≤7 days from enrollment), an extended mycobacterial reference standard (eMRS), and a composite reference standard including clinical evaluation.

Tuberculosis Immunoreactivity Surveillance in Malawi (Timasamala)-A protocol for a cross-sectional Mycobacterium tuberculosis immunoreactivity survey in Blantyre, Malawi.

Tuberculosis (TB) transmission and prevalence are dynamic over time, and heterogeneous within populations. Public health programmes therefore require up-to-date, accurate epidemiological data to appropriately allocate resources, target interventions, and track progress towards End TB goals. Current methods of TB surveillance often rely on case notifications, which are biased by access to healthcare, and TB disease prevalence surveys, which are highly resource-intensive, requiring many tens of thousands of people to be tested to identify high-risk groups or capture trends.

Enhanced tuberculosis diagnosis with computer-aided chest X-ray and urine LAM in adults with HIV admitted to hospital (CASTLE study): A cluster randomised trial.

Background: People with HIV (PHIV) admitted to hospital have high mortality, with tuberculosis (TB) being the major cause of death. Systematic use of new TB diagnostics could improve TB diagnosis and might improve outcomes.

Methods: We conducted a cluster randomised trial among adult PHIV admitted to Zomba Central Hospital, Malawi.

Improving the management of open tibia fractures, Malawi.

Objective: To assess the impact of an open fracture intervention bundle on clinical management and patient outcomes of adults in Malawi with open tibia fractures.

Methods: We conducted a before-and-after implementation study in Malawi in 2021 and 2022 to assess the impact of an open fracture intervention bundle, including a national education course for clinical officers and management guidelines for open fractures. We recruited 287 patients with open tibia fractures.

Decoding muscle-resident Schwann cell dynamics during neuromuscular junction remodeling.

Understanding neuromuscular junction (NMJ) repair mechanisms is essential for addressing degenerative neuromuscular conditions. Here, we focus on the role of muscle-resident Schwann cells in NMJ reinnervation. In young mice, a model of progressive NMJ degeneration, we identified a clear NMJ 'regenerative window' that allowed us to define regulators of reinnervation and crossing mice with -tg mice permitted visualization and analysis of Schwann cells.

Same-day versus rapid ART initiation in HIV-positive individuals presenting with symptoms of tuberculosis: Protocol for an open-label randomized non-inferiority trial in Lesotho and Malawi.

Background: In absence of contraindications, same-day initiation (SDI) of antiretroviral therapy (ART) is recommended for people testing HIV-positive who are ready to start treatment. Until 2021, World Health Organization (WHO) guidelines considered the presence of TB symptoms (presumptive TB) a contraindication to SDI due to the risk of TB-immune reconstitution inflammatory syndrome (TB-IRIS). To reduce TB-IRIS risk, ART initiation was recommended to be postponed until results of TB investigations were available, and TB treatment initiated if active TB was confirmed.

Process Evaluation of Services for HIV-Infected Post-Partum Women and HIV-Exposed Infants in Primary Health Care Blantyre Malawi.

HIV testing among HIV-exposed infants (HEI) in Malawi is below global targets and, affected by low utilisation of health services after birth. We conducted a mixed methods evaluation of the implementation of services for early infant diagnosis (EID) of HIV against national guidelines in Blantyre, Malawi, to inform the development of strategies to improve EID services uptake. We estimated coverage of HEI enrolment in HIV care and HIV testing at 6 weeks through a retrospective data review.

The prevalence of gestational syphilis in Malawi between 2014 and 2022: spatiotemporal modeling of population-level factors.

Background: Mother-to-child transmission of syphilis remains high especially in the WHO AFRO region with a prevalence of 1.62%, resulting in a congenital syphilis rate of 1,119 per 100,000 live births. Elimination efforts can be supported by an understanding of the spatial and temporal changes in disease over time, which can identify priority areas for targeted interventions aimed at reducing transmission.

Impact of active case-finding for tuberculosis on case-notifications in Blantyre, Malawi: A community-based cluster-randomised trial (SCALE).

Active case-finding (ACF) for tuberculosis can help find the "missing millions" with undiagnosed tuberculosis. In a cluster-randomised trial, we investigated impact of ACF on case-notifications in Blantyre, Malawi, where ACF has been intensively implemented following 2014 estimates of ~1,000 per 100,000 adults with undiagnosed TB. Following a pre-intervention prevalence survey (May 2019 to March 2020), constrained randomisation allocated neighbourhoods to either door-to-door ACF (sputum microscopy for reported cough >2 weeks) or standard-of-care (SOC).

Treatment for radiographically active, sputum culture-negative pulmonary tuberculosis: A systematic review and meta-analysis.

Background: People with radiographic evidence for pulmonary tuberculosis (TB), but negative sputum cultures, have increased risk of developing culture-positive TB. Recent expansion of X-ray screening is leading to increased identification of this group. We set out to synthesise the evidence for treatment to prevent progression to culture-positive disease.

Prevalence of bacteriologically-confirmed pulmonary tuberculosis in urban Blantyre, Malawi 2019-20: Substantial decline compared to 2013-14 national survey.

Recent evidence shows rapidly changing tuberculosis (TB) epidemiology in Southern and Eastern Africa, with need for subdistrict prevalence estimates to guide targeted interventions. We conducted a pulmonary TB prevalence survey to estimate current TB burden in Blantyre city, Malawi. From May 2019 to March 2020, 115 households in middle/high-density residential Blantyre, were randomly-selected from each of 72 clusters.